Our past research has shown that the uptake of macromolecules at the surface of tumor cells can be markedly enhanced by polycations of large molecular weight, by phytohemagglutinin and by aggregates or particles which have nothing in common but their supramolecular size. The mechanisms that underlie these membrane effects are not understood in either case. It must be determined whether they are associated with increased pinocytosis and with modifications of other transport functions (e.g., uptake of 2-deoxyglucose, vitamin B12). The finding that polystyrene beads, 0.09 to 5.7 micron in diameter, enhance albumin uptake proportionally to their volume will be extended by using particles of larger sizes and different material (glass, polyacrylamide). In a second line of investigation, carried out simultaneously, all the data from this and prior grant periods which relate to membrane functions of tumor cells will be applied to a systematic search for critical differences in the membrane properties of normal and tumor cells. This comparison is aimed at determining whether non-malignant cells and their malignant variants differ in any of the following ways: uptake of albumin; uptake of a second model protein transported more selectively; effect of any known enhancer on the uptake of two model proteins; cellular uptake of several enhancers; effect of known enhancers upon other transport functions of the cell membrane; relationship between membrane effects and uptake of several enhancers; relationship between membrane effect and volume of supramolecular particles; changes in any of the above parameters caused by temperature, pretreatment with ligands, lectins, solvents, proteolytic enzymes, compounds acting on cell mobility, on adenylcyclase, on macromolecular assembly, and macromolecular synthesis. It is increasingly apparent that malignant growth is causally related to changes in the cell membrane, but no changes common to all tumors have yet been singled out. It is compelling therefore to use data obtained in our study of protein uptake as new tools to probe for critical changes associated with malignant transformation.